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CN-121490147-B - Bionic biological valve

CN121490147BCN 121490147 BCN121490147 BCN 121490147BCN-121490147-B

Abstract

The invention relates to the field of biological materials, in particular to a bionic biological valve. The bionic biological valve is obtained by wrapping a cross-linked extracellular matrix material by a non-cross-linked biological substrate membrane to form a sandwich structure. The basement membrane and the cross-linked extracellular matrix material cooperate to fully play the excellent regeneration and repair performances of the basement membrane and the characteristic of being rich in bioactive factors, effectively promote the growth and adhesion of endothelial cells on the surface of the material, and construct the tissue structure of the simulated natural valve leaflet. The bionic biological valve has excellent calcification resistance, excellent dynamic mechanical stability and compliance, remarkably inhibits abnormal adhesion of platelets and blood cells, greatly improves the recovery and reconstruction efficiency of valve functions, can maintain structural integrity in repeated contraction-expansion cycles, and provides an ideal solution for long-term stable application in physiological environment.

Inventors

  • DAI JING
  • XU YIWEN
  • CHENG WENYUE

Assignees

  • 上海卓阮医疗科技有限公司
  • 卓阮医疗科技（苏州）有限公司

Dates

Publication Date
20260512
Application Date
20260112

Claims (12)

  1. 1. The bionic biological valve is obtained by wrapping a crosslinked extracellular matrix material by a non-crosslinked biological substrate membrane to form a sandwich structure, and is characterized in that the source of the non-crosslinked biological substrate membrane at least comprises a bladder; A transition layer is arranged between the non-crosslinked biological basal membrane and the crosslinked extracellular matrix material, and comprises a biocompatible colloid matrix treated by a coupling agent; The biocompatible colloid matrix is formed by solidifying at least 8-44 mu L/cm 2 of biocompatible colloid matrix dispersion liquid and 1-4 mu L/cm 2 of coupling agent aqueous solution, wherein the biocompatible colloid matrix dispersion liquid at least comprises atelopeptide collagen and 3-17 wt% of gelatin aqueous dispersion liquid.
  2. 2. The biomimetic biological valve of claim 1, wherein the area concentration ratio of the biocompatible colloidal matrix dispersion and the aqueous coupling agent solution is (7-12): 1.
  3. 3. The biomimetic biological valve of any one of claims 1-2, wherein the non-crosslinked biological substrate membrane and crosslinked extracellular matrix material have different sources.
  4. 4. The biomimetic biological valve of claim 1, wherein the preparation of the cross-linked extracellular matrix material comprises at least decellularization and cross-linking.
  5. 5. The biomimetic biological valve of claim 4, wherein the cross-linked extracellular matrix material is subjected to at least two discrete peroxide treatments during decellularization.
  6. 6. The biomimetic biological valve of claim 4, wherein the cross-linked extracellular matrix material decellularization is subjected to at least a sequential treatment process of a first peroxide treatment, a surfactant and a second peroxide treatment.
  7. 7. The biomimetic biological valve of claim 5, wherein the peroxide is selected from one or more of peracetic acid, peroxypropionic acid, hydrogen peroxide, sodium peroxide.
  8. 8. The biomimetic biological valve of claim 6, wherein the first peroxide is hydrogen peroxide and the second peroxide is peracetic acid and/or peroxypropionic acid.
  9. 9. The biomimetic biological valve according to any one of claims 5-8, wherein during decellularization of the cross-linked extracellular matrix material, the peroxide treatment has been preceded by an initial treatment with an enzyme and an aqueous alcohol solution.
  10. 10. The biomimetic biological valve of claim 4, wherein cross-linking is performed using a homobifunctional cross-linker during cross-linking to prepare the cross-linked extracellular matrix material.
  11. 11. The biomimetic biological valve of claim 4 or 10, wherein the preparation of the cross-linked extracellular matrix material further comprises a soaking treatment in a capping agent solution after cross-linking washing.
  12. 12. Use of the biomimetic biological valve according to claim 1 for the preparation of heart valve, vascular valve materials.

Description

Bionic biological valve Technical Field The invention relates to the field of biological materials, in particular to a bionic biological valve. Background Heart valve replacement is the main means for treating valvular heart disease at present, heart valves commonly used in valve replacement at present are mainly divided into mechanical heart valves and biological heart valves, mechanical valves have high mechanical strength but poor biocompatibility, long-term anticoagulation treatment needs to be matched, and biological valves have good compatibility and hemodynamic performance and better treatment effect, so that the heart valves are the main current products at present. Conventionally, pericardial tissues treated by glutaraldehyde are used as biological valves, however, the tissues cannot regenerate cells, and the tissues which cannot regenerate cannot respond to damage such as abrasion, fatigue or calcification through a self-repairing mechanism in long-term use, and micro cracks can be enlarged while the performance gradually declines, so that the valve is accelerated to fail, and the service life is very limited. The biological valve disclosed in the patent No. CN115920132A is a cross-linked amniotic membrane wrapping cross-linked pericardium structure, and the wrapping structure is further subjected to integral cross-linking under the initiation of ammonium persulfate and sodium bisulphite so as to improve the binding force between different membrane layers, and the inherent defect of pericardium is improved by utilizing the function of the regenerated cells of the amniotic membrane. However, the mechanical strength of the amniotic membrane is insufficient, as described in the CN115920132a patent, which is generally crosslinked to achieve the mechanical properties required for the valve. Secondly, the amniotic membrane as a surface layer is crosslinked to increase the calcification risk, and the amniotic membrane has high source cost, so that mass production is difficult to realize. Disclosure of Invention In order to overcome the problems, the invention uses the non-crosslinked biological basement membrane to wrap the crosslinked extracellular matrix, so that the crosslinked extracellular matrix with calcification risk after crosslinking is encapsulated, the biological valve has a regeneration function, and meanwhile, the calcification risk is not increased, but the biological valve has a certain calcification resistance capacity, and has the application prospect of mass production. The invention provides a bionic biological valve, which is obtained by wrapping a cross-linked extracellular matrix material by a non-cross-linked biological basement membrane to form a sandwich structure. The bionic biological valve provided by the first aspect of the invention is characterized in that a transition layer is arranged between the uncrosslinked biological substrate membrane and the crosslinked extracellular matrix material, and the transition layer comprises a biocompatible colloid matrix treated by a coupling agent. The biocompatible colloid matrix is formed by solidifying at least 8-50 mu L/cm 2 of biocompatible colloid matrix dispersion liquid and 1-10 mu L/cm 2 of coupling agent aqueous solution. As an example, the biocompatible colloidal matrix is formed by solidifying at least 8 to 50. Mu.L/cm 2 of a dispersion of the biocompatible colloidal matrix and 1 to 7. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, the biocompatible colloidal matrix is formed by solidifying at least 8 to 45. Mu.L/cm 2 of a dispersion of the biocompatible colloidal matrix and 1 to 10. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, the biocompatible colloidal matrix is formed by solidifying at least 8 to 45. Mu.L/cm 2 of a dispersion of the biocompatible colloidal matrix and 1 to 7. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, the biocompatible colloidal matrix is formed by solidifying at least 8 to 50. Mu.L/cm 2 of a dispersion of the biocompatible colloidal matrix and 1 to 5. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, the biocompatible colloidal matrix is formed by solidifying at least 8 to 45. Mu.L/cm 2 of a dispersion of the biocompatible colloidal matrix and 1 to 5. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, a biocompatible colloidal matrix is formed by solidifying at least 8 to 44. Mu.L/cm 2 of a dispersion of a biocompatible colloidal matrix and 1 to 5. Mu.L/cm 2 of an aqueous solution of a coupling agent. As an example, a biocompatible colloidal matrix is formed by solidifying at least 8 to 44. Mu.L/cm 2 of a dispersion of a biocompatible colloidal matrix and 1 to 4. Mu.L/cm 2 of an aqueous solution of a coupling agent. The transition layer is formed by sequentially superposing and solidifying all layers after the biocompatible colloid matrix dispersion liquid and the coupling agent aqueous solution a